Why do some people get cancer while others don’t? Scientists have one explanation

ADELAIDE, Australia — Your risk of cancer may be linked to something deep inside your body. Australian researchers have established a significant link between a person’s cancer risk and the functions of circular RNAs (circular genetic fragments) found in our cells. The results reveal that specific circular RNAs can bind to DNA in our cells, leading to DNA mutations that can cause cancer. Known as “ER3D” (endogenous RNA-directed DNA damage), this revolutionary discovery marks a new era in medical and molecular biology research.

“This is the first example of a genetic molecule found in many individuals that has the ability to mutate our own DNA and drive cancer from within. This breakthrough opens doors to using these molecules as therapeutic targets and early disease markers , when the chances of successful treatment are higher,” explains Professor Vanessa Conn, who heads the Circular RNAs in Cancer Laboratory at the Flinders Health and Medical Research Institute, in a media release.

To uncover the link between circular RNAs and cancer, researchers compared the neonatal blood samples of infants who later developed acute leukemia with those who did not have any blood disorders. They discovered that a specific circular RNA was present at significantly higher levels in infants who developed leukemia, even before the onset of symptoms. These findings suggest that the abundance of circular RNA molecules in certain individuals’ cells is a major determinant of why some individuals develop cancer-causing genes or oncogenes while others do not.

Circular RNAs have the ability to bind to DNA at different sites in different cells. By binding to specific sites on DNA, they initiate changes that result in DNA breaks that the cell must repair in order to survive. However, this repair process is not always flawless and can lead to small mutations, akin to misspelled words in a book, or more severe cases, significant and devastating mutations.

In addition, circular RNAs can also change the physical location of the damaged DNA in the cell nucleus, causing two different regions of the DNA to fuse together during the repair process, like merging the pages of different books. Prof. Conn notes that multiple circular RNAs appear to work in partnership, causing breaks at multiple DNA sites. This process, called chromosomal translocation, poses a significant challenge to cells as it results in gene fusions that can transform normal cells into cancer cells. The researchers demonstrated this phenomenon in two different cell types, observing its role in the rapid onset of aggressive leukemia.

The gene fusions resulting from the action of circular RNAs occur at well-known mutational “hotspots” in leukemia. This has critical implications for Australia, which has the highest incidence of leukemia worldwide, with approximately 35,000 Australians currently living with the disease. These gene fusions have long been used by physicians worldwide to guide treatment decisions because of their negative impact on patient prognosis.

Dr. Conn emphasizes that ER3D is not exclusive to leukemia; the process extends to other types of cancer and human diseases. The research team at Flinders University is dedicated to further investigating the role of circular RNAs in cancer and other diseases, paving the way for improved understanding and potential therapeutic breakthroughs.

The study is published in the journal Cancer cell.